NDLI: Truncating the i-leader open reading frame enhances release of human adenovirus type 5 in glioma cells

Content Provider	Springer Nature : BioMed Central
Author	van den Hengel, Sanne K de Vrij, Jeroen Uil, Taco G Lamfers, Martine L Sillevis Smitt, Peter AE Hoeben, Rob C
Abstract	Background The survival of glioma patients with the current treatments is poor. Early clinical trails with replicating adenoviruses demonstrated the feasibility and safety of the use of adenoviruses as oncolytic agents. Antitumor efficacy has been moderate due to inefficient virus replication and spread. Previous studies have shown that truncation of the adenovirus i-leader open reading frame enhanced cytopathic activity of HAdV-5 in several tumor cell lines. Here we report the effect of an i-leader mutation on the cytopathic activity in glioma cell lines and in primary high-grade glioma cell cultures. Results A mutation truncating the i-leader open reading frame was created in a molecular clone of replication-competent wild-type HAdV-5 by site-directed mutagenesis. We analyzed the cytopathic activity of this RL-07 mutant virus. A cell-viability assay showed increased cytopathic activity of the RL-07 mutant virus on U251 and SNB19 glioma cell lines. The plaque sizes of RL-07 on U251 monolayers were seven times larger than those of isogenic control viruses. Similarly, the cytopathic activity of the RL-07 viruses was strongly increased in six primary high-grade glioma cell cultures. In glioma cell lines the RL-07 virus was found to be released earlier into the culture medium. This was not due to enhanced viral protein synthesis, as was evident from equivalent E1A, Fiber and Adenovirus Death Protein amounts, nor to higher virus yields. Conclusion The cytopathic activity of replicating adenovirus in glioblastoma cells is increased by truncating the i-leader open reading frame. Such mutations may help enhancing the antitumor cytopathic efficacy of oncolytic adenoviruses in the treatment of glioblastoma.
Related Links	https://virologyj.biomedcentral.com/counter/pdf/10.1186/1743-422X-8-162.pdf
Ending Page	9
Page Count	9
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/1743-422X-8-162
Journal	Virology Journal
Issue Number	1
Volume Number	8
Language	English
Publisher	BioMed Central
Publisher Date	2011-04-11
Access Restriction	Open
Subject Keyword	Virology glioma gene therapy adenovirus i-leader oncolytic virus
Content Type	Text
Resource Type	Article
Subject	Virology Infectious Diseases
Journal Impact Factor	4/2023
5-Year Journal Impact Factor	3.8/2023

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